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D C Kaslow

Publications and source records attributed to D C Kaslow.

121 records · Page 7Linked to original sources
PubMed1989

Comparison of the primary structure of the 25 kDa ookinete surface antigens of Plasmodium falciparum and Plasmodium gallinaceum reveal six conserved regions.

The gene encoding the 25 kDa ookinete surface antigen (Pgs25) of Plasmodium gallinaceum has been cloned using an oligonucleotide probe directed against one of the EGF-like domains of the P. falciparum 25 kDa ookinete surface antigen (Pfs25). The Pgs25 gene codes for a polypeptide of 215 amino acids, two amino residues less than Pfs25. The deduced amino acid sequence contains a putative signal sequence at the amino-terminus, four tandemly repeated EGF-like domains, and a hydrophobic region at the carboxyl-terminus. By comparing Pgs25 with Pfs25, six conserved regions, consisting of six or more amino acid residues, have been identified. Most of the conserved regions are outside EGF-like core consensus sequences. The most striking conservation is the spacing of the cysteines.

Amino Acid Sequence↗
PubMed1988

A vaccine candidate from the sexual stage of human malaria that contains EGF-like domains.

Malaria vaccines are being developed against different stages in the parasite's life cycle, each increasing the opportunity to control malaria in its diverse settings. Sporozoite vaccines are designed to prevent mosquito-induced infection; first generation recombinant or synthetic peptide vaccines have been tested in humans. Asexual erythrocytic stage vaccines, developed to prevent or reduce the severity of disease, have been tested in animals and in humans. A third strategy is to produce sexual stage vaccines that would induce antibodies which would prevent infection of mosquitoes when ingested in a bloodmeal containing sexual stage parasites. Although not directly protective, the sexual stage vaccine combined with a sporozoite or asexual stage vaccine (protective component) could prolong the useful life of the protective component by reducing transmission of resistant vaccine-induced mutants. In areas of low endemnicity, the sexual stage vaccine could reduce transmission below the critical threshold required to maintain the infected population, thereby assisting in the control or eradication of malaria. Transmission of Plasmodium falciparum, the major human malaria, can be blocked by monoclonal antibodies against three sexual stage-specific antigens. We have cloned the gene encoding the surface protein of relative molecular mass Mr 25,000 (25K; Pfs25), expressed on zygotes and ookinetes of P. falciparum. The deduced amino-acid sequence consists of a signal sequence, a hydrophobic C-terminus, and four tandem epidermal growth factor EGF-like domains.

Amino Acid Sequence↗
PubMed1987

Signal sequence and DNA-mediated expression of human lysosomal alpha-galactosidase A.

Twelve complementary DNA clones for human lysosomal alpha-galactosidase A were isolated from an Okayama-Berg library constructed from SV40-transformed human fibroblasts. The identity of these clones was confirmed by complete colinearity of the nucleotide-deduced amino acid sequence with that determined by direct chemical sequencing of human placental alpha-galactosidase A. Hybridization of the alpha-galactosidase A cDNA to genomic DNA from individuals with varying numbers of X chromosomes as well as from interspecies somatic-cell hybrids showed only a single locus in the genome at Xq 13.1-Xq 22. One cDNA clone (pcD-AG210) contained the complete coding sequence for both the signal peptide and mature alpha-galactosidase A. The signal peptide of 31 amino acids contains the expected hydrophobic domains consisting of Leu-Gly-Cys-Ala-Leu-Ala-Leu and Phe-Leu-Ala-Leu-Val and has Ala at the signal peptidase cleavage site. Twelve out of fifteen G residues flanking the 5' end of the cDNA in pcD-AG210 were removed and the truncated fragment was ligated into the original vector. This construct, pcD-AG502, encoded enzymatically active human alpha-galactosidase A in monkey COS cells.

Amino Acid Sequence↗
PubMed1987

Molecular studies of marsupial X chromosomes reveal limited sequence homology of mammalian X-linked genes.

To explore the extent to which the X chromosome has been conserved during mammalian evolution, we compared six loci that are X-linked in the human genome with the corresponding genes of the North American marsupial, the Virginia opossum (Didelphis virginiana). Our analysis shows that in the opossum genome there are sequences highly homologous to those of human cDNAs for housekeeping genes, glucose-6-phosphoribosyltransferase (HPRT), phosphoglycerate kinase A (PGK1), and alpha-galactosidase A (GLA). However, ornithine transcarbamylase and blood clotting Factor IX--tissue-specific genes that are X-linked in eutherians mammals--have no highly conserved homologs in the marsupial genome. By cloning opossum G6PD and HPRT, we found that these genes are X-linked in the opossum and that homologous sequences are limited to coding regions. As all genomic fragments hybridizing with the human GLA probe show dosage effects, it is likely that the opossum counterpart is X-linked. Finally, the pattern of hybridization suggests that the autosomal pseudogenes of HPRT and PGK1 in the opossum have remained highly homologous to the human X-linked genes.

Animals↗
PubMed1987

DNA methylation stabilizes X chromosome inactivation in eutherians but not in marsupials: evidence for multistep maintenance of mammalian X dosage compensation.

In marsupials and eutherian mammals, X chromosome dosage compensation is achieved by inactivating one X chromosome in female cells; however, in marsupials, the inactive X chromosomes is always paternal, and some genes on the chromosome are partially expressed. To define the role of DNA methylation in maintenance of X chromosome inactivity, we examined loci for glucose-6-phosphate dehydrogenase and hypoxanthine phosphoribosyltransferase in a North American marsupial, the opossum Didelphis virginiana, by using genomic hybridization probes cloned from this species. We find that these marsupial genes are like their eutherian counterparts, with respect to sex differences in methylation of nuclease-insensitive (nonregulatory) chromatin. However, with respect to methylation of the nuclease-hypersensitive (regulatory) chromatin of the glucose-6-phosphate dehydrogenase locus, the opossum gene differs from those of eutherians, as the 5' cluster of CpG dinucleotides is hypomethylated in the paternal as well as the maternal gene. Despite hypomethylation of the 5' CpG cluster, the paternal allele, identified by an enzyme variant, is at best partially expressed; therefore, factors other than methylation are responsible for repression. In light of these results, it seems that the role of DNA methylation in eutherian X dosage compensation is to "lock in" the process initiated by such factors. Because of similarities between dosage compensation in marsupials and trophectoderm derivatives of eutherians, we propose that differences in timing of developmental events--rather than differences in the basic mechanisms of X inactivation--account for features of dosage compensation that differ among mammals.

Animals↗
PubMed1986

Comparison of factor IX methylation on human active and inactive X chromosomes: implications for X inactivation and transcription of tissue-specific genes.

Maintenance of dosage compensation for housekeeping genes on the human X chromosome is mediated through differential methylation of clustered CpG nucleotides associated with these genes. To determine if methylation has a role in maintaining inactivity of X-linked genes which show tissue-specific expression, we examined the locus for blood clotting Factor IX. The analysis encompassed 91% of the HpaII and HhaI sites in the 41-kb region that includes the presumed promoter region, 5 kb of 5'- and 4 kb of 3'-flanking sequences. Although there are sex differences in methylation of the locus in leukocytes, the methylation pattern in liver, where the gene is expressed, is essentially the same for loci on the active and inactive X chromosome. The lack of differences in methylation of active and inactive genes makes it unlikely that methylation within the locus has a role in expression of the Factor IX gene. These findings, along with the absence of clustered CpG dinucleotides within the Factor IX locus, suggest that functional differences in DNA methylation related to X chromosome dosage compensation may be limited to CpG clusters. In any event, dosage compensation seems to be maintained regionally, rather than locus by locus.

Factor IX↗
PubMed1985

Incomplete X chromosome dosage compensation in chorionic villi of human placenta.

Studies of glucose-6-phosphate dehydrogenase (G6PD) in heterozygous cells from chorionic villi of five fetal and one newborn placenta show that the locus on the allocyclic X is expressed in many cells of this trophectoderm derivative. Heterodimers were present in clonal populations of cells with normal diploid karyotype and a late replicating X chromosome. The expression of the two X chromosomes was unequal, based on ratios of homodimers and heterodimers in clones. Studies of DNA, digested with Hpa II and probed with cloned genomic G6PD sequences, indicate that expression of the locus in chorionic villi is associated with hypomethylation of 3' CpG clusters. These findings suggest that dosage compensation, at least at the G6PD locus, has not been well established or maintained (or both) in placental tissue. Furthermore, the active X chromosome in these human cells of trophoblastic origin can be either the paternal or maternal one; therefore, paternal X inactivation in extraembryonic lineages is not an essential feature of mammalian X dosage compensation.

Cells, Cultured↗
PubMed1983

The developmental effects of prostaglandin D2 on the pulmonary and systemic circulations in the newborn lamb.

Prostaglandin D2 (PGD2) lowers pulmonary arterial blood pressure without changing systemic arterial blood pressure in fetal and newborn lambs but increases pulmonary arterial pressure in older animals. We investigated the effect of PGD2 on the circulation in 15 newborn lambs, some studied intermittently from 1 to 30 days of age, with induced pulmonary arterial hypertension. PGD2 was infused intravenously in doses of 1 to 25 micrograms/kg per min. During the first 3 days of life, a 5 micrograms/kg per min infusion decreased mean pulmonary arterial pressure by 33.9%, increased mean systemic arterial pressure by 11.5% and increased cardiac output by 7.3%. After 15 days of age there was a 10.7% increase in mean pulmonary arterial pressure, a 1.8% decrease in mean systemic arterial pressure and a 6.1% increase in cardiac output. Pulmonary vascular resistance decreased by 38.2% in the first 3 days of life but increased by 9.9% after 15 days of life. With this progressive pulmonary vasoconstriction, there was systemic vasodilation with advancing age. Similar age specific effects were seen with 1 and 25 micrograms/kg per min infusions. The specificity of PGD2 for the pulmonary circulation and the attenuation of its vasodilating properties during the first week of life suggests that PGD2 may be important in the regulation of pulmonary vascular resistance and pulmonary blood flow during the immediate perinatal period.

Animals↗
PubMedDate not supplied

Short report: IgG1/IgG3 antibody responses to various analogs of recombinant ypfmsp119--a study in immune adults living in areas of Plasmodium falciparum transmission.

To further characterize protective-type (IgG1/IgG3) antibody responses to Plasmodium falciparum blood stage in putatively immune individuals' plasma, we have tested for various analogs of the 19 kDa C-terminus of the MSP1 antigen obtained as secreted recombinant proteins from Saccharomyces cerevisiae. One of four proteins was then identified on the basis of consistent IgG3, along with less variable IgG1 recognition. This protein has thus been selected for further functional assays of IgG1/IgG3 antibodies.

Animals↗